Mutation in Codon 200 and Polymorphism in Codon 129 of the Prion
Protein Gene in Libyan Jews with Creutzfeldt-Jakob Disease
R. Gabizon, H. Rosenman, Z. Meiner, I. Kahana, E. Kahana,
Y. Shugart, J. Ott, S.B. Prusiner
Philosophical Transactions of the Royal Society of London - Series B:
Biological Sciences
343(1306),385--390 (1994 Mar 29)
Abstract
Various mutations in the prion protein (PrP) gene are associated
with Creutzfeldt-Jakob disease (CJD), a transmissible fatal
neurodegenerative disorder. Among Libyan Jews, CJD is a familial
disease with an incidence about 100 times higher than the worldwide
population. CJD in this community segregates with a point mutation
at codon 200 of the PrP gene which causes the substitution of lysine
for glutamate. This mutation was found in all definitely affected
individuals and yields a maximum lod score of 4.85. Some healthy
elderly mutation carries above 65 years of age were identified,
suggesting partial penetrance. Homozygous patients have the same
disease pattern and age of onset as heterozygous patients, which
argues that CJD associated with the codon 200 lysine mutation is a
true dominant disorder. In the caucasian population, Palmer et al.
(1991) reported an association between homozygosity in a polymorphic
site at codon 129 of the PrP gene, coding for either valine or
methionine, with a tendency to acquire the sporadic or iatrogenic
forms of CJD, as well as with disease age of appearance in the
genetic type. The incidence of the polymorphism at codon 129 in the
control Libyan population is similar to the one found in the
caucasian population. In the Libyan CJD patients, the codon 200
mutation is within a Met129-encoding allele. The incidence of the
Met allele is significantly higher in the affected pedigrees than in
the control Libyan population; however, no difference was detected
between CJD patients, codon 200 healthy carriers, and their normal
family members.(ABSTRACT TRUNCATED AT 250 WORDS)
